In the peripheral nervous system, specialized glial cells called Schwann cells exist in intimate association with neuronal axons. Myelinating Schwann cells iteratively wrap their membrane around a single axonal segment to generate the myelin sheath, while Remak Schwann cells envelop multiple small caliber axons. Both types of Schwann cells arise from a common immature Schwann cell precursor, and although important questions remain unanswered, far more is known about the molecular mechanisms that govern the development of myelinating Schwann cells. The study of Remak Schwann cells has been significantly hindered by a paucity of tools - few specific markers are known, and most of these are also expressed by immature Schwann cells. Additionally, there are no transgenic mice that permit genetic deletion in Remak Schwann cells. The main goals of this proposal are to test a bacTRAP toolset for PNS glia, and to define the molecular signature of mature Remak Schwann cells. The secondary goals of this proposal, using data obtained from the bacTRAP analysis, are to generate test new reagents for reliably targeting transgenes to Remak Schwann cells, including Cre recombinase for conditional gene deletion. PUBLIC HEALTH RELEVANCE: An exquisite example of specialized cell-cell interactions in the nervous system is the intimate association of glial cells with axons. In the peripheral nerve, Remak Schwann cells are an understudied class of glial cell, although it is increasingly clear that these cells are critical mediators of nerve regeneration and disease pathology. In this proposal, we will develop much-needed tools for the study of Remak Schwann cells, including new tools for measuring their gene expression, new molecular markers and reagents for generating transgenic mice for Cre mediated recombination in this cell type.